Stopping The Aging Cliff - New Study Backing C15:0

Healthy Aging

How C15:0 Could Outrank The Longevity Leader
(aka Rapamycin)

What if there was a foundational nutrient that was arguably better than a leading longevity molecule at stopping a critical cliff in the aging process? In a just-published paper by Kalfin et al., they lay out a methodical, science-backed argument of C15:0 (aka pentadecanoic acid) to slow age-related female infertility, and they center their evidence around C15:0’s multiple paths to safely inhibit mTOR in humans. Doubling down on their argument, they share how use of C15:0 in humans to slow a core component of aging is more feasible than rapamycin, a molecule with the most laboratory-based evidence of extending longevity in mammals. Let’s dive in.

I’m in. But first, what’s mTOR, and is rapamycin really still the leading longevity molecule?

A few weeks ago, we shared the KEGG Human Longevity Regulating Pathway, which maps out various biological paths that lead to the holy grail – healthy longevity. One of the most promising pathways is inhibition of mTOR, which stands for the “mechanistic Target Of Rapamycin”.

When you have your own longevity pathway named after you, that’s a pretty good indicator that rapamcyin is an understood enabler of longevity – at least in the lab. As explained by Kalfin et al.:

• mTOR likes to rev our cells up, which can be good. Unless it is revving up cells that aren’t working well and should be retired and recycled. Normally, dysfunctional cells should be put to rest using a process called autophagy.
• As we age, mTOR becomes overactivated. This overactivation results in “zombie cells” that create a pro-inflammatory and anti-mitochondrial environment within our tissues. The result? Accelerated aging throughout our body.
• Rapamycin is a natural molecule made by the bacterium, Streptomyces hygroscopius, which was first discovered on Easter Island. “Rapa” pays homage to rapamycin’s hometown (Easter Island is also called Rapa Nui). “Mycin” was based on rapamycin’s initially discovered antifungal superpower.
• Ends up, rapamycin also inhibits mTOR. By inhibiting mTOR, and based on many (many) studies over decades, Kalfin et al. describe rapamycin as “the most extensively validated pharmacological intervention for lifespan extension in mammals… firmly establishing mTOR inhibition as one of the most robust and reproducible longevity-promoting strategies in mammalian aging research.”

Here’s the rub. Rapamycin is so good at specifically targeting mTOR, that with chronic use, it inhibits both mTOR (which is good) and mTORC2 (which is bad). This is because mTORC2 keeps our insulin and glucose metabolism happy.

Alas, mTOR is also a strong immunosuppressant. Which means that it can suppress immune responses that we need to fight off infections.

For these reasons, continuous, chronic use of rapamycin for the purposes of extending human longevity has become increasingly untenable. It’s a holy grail that’s too hot to handle.

An aging cliff focus: female infertility.

Let’s bring the conversation back to healthy aging. Women have a very specific biological aging clock, which is based on how many functioning oocytes (eggs) remain in her ovaries over time. While it has long been known that those happy oocyte numbers go down from millions to thousands to none with age, a landmark study last year by Li et al. comprehensively described a literal aging cliff that happens in women around the age of 34 years. 

As it relates to oocytes, Li et al. and others have shown that over 2000 genes governing the following collapse as part of this aging cliff:

• Healthy protein production
• Healthy chromosome maintenance
• DNA repair
• Antioxidant defense
• Protection against a cell death called ferroptosis
• Functioning mitochondria

If you are a woman who is 40+ (and certainly 50+), you know exactly how this cliff feels. This is because these aging-related changes affect not only the oocytes, but our entire body.

As reviewed by Kalfin et al., the body of research around age-related infertility points to overactivation of mTOR not just as a component of this aging cliff – but as a core tenant.

Rapamycin as a blessing and curse for aging-related infertility

Understanding the above, inhibiting mTOR has been studied as a means to stop or slow this aging cliff. In their review, Kalfin et al. share studies in which rapamcyin has been shown to:

• Preserve the ovarian reserve and extend reproductive lifespan in rodents
• Reduce mTOR-dependent premature loss of ovarian reserve in rodents
• Slow ovarian aging in rodents as effectively as caloric restriction (another longevity-enabler)
• Increase successful IVF-related pregnancy rates in women (50% vs. 28% success compared to non-treated controls)

Despite these wins, the risks of longer-term rapamycin use and the need for washout periods to protect healthy pregnancies have been deemed too great to safely use rapamycin to help with age-related infertility.

All of this background set the stage for Kalfir et al.’s evidence-based argument for C15:0 as a safe and effective means to naturally inhibit mTOR and protect against aging-related breakdown – with a focus on protecting female fertility with age.